title: The curry spice curcumin attenuates beta-amyloid-induced toxicity through beta-catenin and PI3K signaling in rat organotypic hippocampal slice culture.
abstract: OBJECTIVE
  Accumulating evidence indicates that curcumin potently protects against beta-amyloid (Abeta) due to its oxygen free radicals scavenging and anti-inflammatory properties. However, cellular mechanisms that may underlie the neuroprotective effect of curcumin in Abeta-induced toxicity are not fully understood yet. The present study was undertaken to investigate the mechanisms involved in neuroprotective effects of curcumin, particularly involving Wnt/beta-catenin and PI3K pathways.
  
  
  METHODS
  Organotypic hippocampal slice cultures were treated with curcumin and exposed to Abeta1-42 for 48 hours. Synaptic dysfunction, cell death, ROS formation, neuroinflammation and beta-catenin, Akt, and GSK-3beta phosphorylation were measured to determine the effects of curcumin against Abeta toxicity.
  
  
  RESULTS
  Curcumin significantly attenuated Abeta-induced cell death, loss of synaptophysin, and ROS generation. Furthermore, curcumin was able to decrease IL-6 release and increase IL-10 release, and prevented glial activation. The phosphorylation of beta-catenin was avoided and the levels of free beta-catenin were increased by curcumin to promote cell survival upon treatment with Abeta. Curcumin, in the presence of Abeta, activated Akt which in turn phosphorylates GSK-3beta, and resulted in the inhibition of GSK-3beta. The presence of LY294002, an inhibitor of PI3K pathway, blocked the pro-survival effect of curcumin.
  
  
  CONCLUSIONS
  These results reinforce the neuroprotective effects of curcumin on Abeta toxicity and add some evidence that its mechanism may involve beta-catenin and PI3K signaling pathway in organotypic hippocampal slice culture.
authors.affiliation: Federal University of Rio Grande do Sul, Porto Alegre, RS, Brazil.
authors.forename: Juliana Bender
authors.initials: JB
authors.lastname: Hoppe
authors.forename: Rudimar Luiz
authors.initials: RL
authors.lastname: Frozza
authors.forename: Elisa Nicoloso Simões
authors.initials: EN
authors.lastname: Pires
authors.forename: André Bevilacqua
authors.initials: AB
authors.lastname: Meneghetti
authors.forename: Christianne
authors.initials: C
authors.lastname: Salbego
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D003474:Curcumin / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism*; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000633:toxicity; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D016708:Synaptophysin / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D002867:Chromones; D015850:Interleukin-6; D009025:Morpholines; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D016708:Synaptophysin; C569016:Syp protein, rat; C075222:amyloid beta-protein (1-42); D051176:beta Catenin; D016753:Interleukin-10; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D003474:Curcumin